13,14-Dihydro-PGD1, analogs

ABSTRACT

Prostaglandin analogs with the following cyclopentane ring structure: ##STR1## are disclosed along with intermediates useful in their preparation and processes for their preparation. These analogs are useful for the same pharmacological purposes as the prostaglandins, particularly and especially as blood platelet aggregation inhibitors.

The present application is a divisional application of Ser. No. 614,242,filed Sep. 17, 1975, now issued as U.S. Pat. No. 4,016,184, on Apr. 5,1977.

The present invention relates to prostaglandin analogs for which theessential material constituting a disclosure therefor is incorporated byreference here from U.S. Pat. No. 4,016,184, issued Apr. 5, 1977.

I claim:
 1. A prostaglandin analog of the formula ##STR2## wherein g isone, 2, or 3; WHEREIN M₁ is ##STR3## or ##STR4## wherein R₅ and R₆ arehydrogen or methyl, with the proviso that one of R₅ and R₆ is methylonly when the other is hydrogen;Wherein L₁ is ##STR5## or a mixture of##STR6## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being thesame or different, with the proviso that one of R₃ and R₄ is fluoro onlywhen the other is hydrogen or fluoro; Wherein m is one to 5, inclusive;and Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substituted with one, two, or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 2. A compound according to claim 1,wherein g is one.
 3. A compound according to claim 2, wherein m is
 3. 4.A compound according to claim 3, wherein at least one of R₃ and R₄ isfluoro.
 5. A compound according to claim 4, wherein R₃ and R₄ are bothfluoro.
 6. A compound according to claim 5, wherein R₅ and R₆ arehydrogen.
 7. 2,2,16,16-Tetrafluoro-13,14-dihydro-PGD₁, a compoundaccording to claim
 6. 8. A compound according to claim 3, wherein atleast one of R₃ and R₄ is methyl.
 9. A compound according to claim 8,wherein R₃ and R₄ are both methyl.
 10. A compound according to claim 9,wherein R₅ and R₆ are both hydrogen. 11.2,2-Difluoro-16,16-dimethyl-13,14-dihydro-PGD₁, a compound according toclaim
 10. 12. A compound according to claim 3, wherein R₃ and R₄ areboth hydrogen.
 13. A compound according to claim 12, wherein R₅ and R₆are both hydrogen.
 14. 2,2-Difluoro-13,14-dihydro-PGD₁, a compoundaccording to claim
 13. 15. A compound according to claim 12, wherein R₅is methyl.
 16. 2,2-Difluoro-15-methyl-13,14-dihydro-PGD₁, a compoundaccording to claim
 15. 17. A compound according to claim 12, wherein R₆is methyl.
 18. 2,2-Difluoro-13,14-dihydro-PGD₁, 15-methyl ether, acompound according to claim
 17. 19. A prostaglandin analog of theformula ##STR7## wherein g is one, 2, or 3; wherein M₁ is ##STR8## or##STR9## wherein R₅ and R₆ are hydrogen or methyl, with the proviso thatone of R₅ and R₆ is methyl only when the other is hydrogen;wherein L₂ is##STR10## or a mixture of ##STR11## and ##STR12## wherein R₃ and R₄ arehydrogen or fluoro, being the same or different, with the proviso thatat least one of R₃ and R₄ is fluoro; wherein m is one to 5, inclusive;and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substitutes with one, two, or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 20. A compound according to claim19, wherein g is
 3. 21. A compound according to claim 20, wherein m is3.
 22. A compound according to claim 21, wherein R₃ and R₄ are bothfluoro.
 23. A compound according to claim 22, wherein R₅ and R₆ arehydrogen.
 24. 2a,2b-Dihomo-16,16-difluoro-13,14-dihydro-PGD₁, a compoundaccording to claim
 23. 25. A compound according to claim 19, wherein gis one.
 26. A compound according to claim 25, wherein m is
 3. 27. Acompound according to claim 26, wherein both R₃ and R₄ are fluoro.
 28. Acompound according to claim 27, wherein R₅ and R₆ are hydrogen. 29.16,16-Difluoro-13,14-dihydro-PGD₁, a compound according to claim
 28. 30.A prostaglandin analog of the formula ##STR13## wherein g is one, 2, or3; wherein M₂ is ##STR14## or ##STR15## wherein L₃ is ##STR16## or amixture of ##STR17## and ##STR18## wherein R₃ and R₄ are hydrogen ormethyl, being the same or different;wherein m is one to 5, inclusive;and wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substituted with one, two, or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 31. A compound according to claim30, wherein g is one.
 32. A compound according to claim 31, wherein m is3.
 33. A compound according to claim 32, wherein at least one of R₃ andR₄ is methyl.
 34. A compound according to claim 33, wherein R₃ and R₄are both methyl.
 35. A compound according to claim 32, wherein R₃ and R₄are hydrogen.
 36. 13,14-Dihydro-PGD₁, 15-methyl ether, a compoundaccording to claim
 35. 37. A prostaglandin analog of the formula##STR19## wherein g is one, 2, or 3; wherein M₃ is ##STR20## or##STR21## wherein R₅ is hydrogen or methyl; wherein L₄ is ##STR22####STR23## or a mixture of ##STR24## and ##STR25## wherein R₃ and R₄ arehydrogen or methyl, being the same or different, with the proviso thatone of R₃ and R₄ is methyl;wherein m is one to 5, inclusive; and whereinR₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkylof 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms,inclusive, phenyl, phenyl substituted with one, two, or three chloro oralkyl of one to 3 carbon atoms, inclusive, or a pharmacologicallyacceptable cation.
 38. A compound according to claim 37, wherein g is 3.39. A compound according to claim 38, wherein m is
 3. 40. A compoundaccording to claim 39, wherein R₃ and R₄ are both methyl.
 41. A compoundaccording to claim 40, wherein R₅ is hydrogen. 42.2a,2b-Dihomo-16,16-dimethyl-13,14-dihydro-PGD₁, a compound according toclaim
 41. 43. A compound according to claim 37, wherein g is one.
 44. Acompound according to claim 43, wherein m is
 3. 45. A compound accordingto claim 44, wherein R₃ and R₄ are both methyl.
 46. A compound accordingto claim 45, wherein R₅ is hydrogen. 47.16,16-Dimethyl-13,14-dihydro-PGD₁, a compound according to claim
 46. 48.A prostaglandin analog of the formula ##STR26## wherein g is one, 2, or3; wherein M₄ is ##STR27## or ##STR28## wherein m is one to 5; andwherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive,cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbonatoms, inclusive, phenyl, phenyl substituted with one, two or threechloro or alkyl of one to 3 carbon atoms, inclusive, or apharmacologically acceptable cation.
 49. 15-methyl-13,14-dihydro-PGD₁, acompound according to claim 48.